is indicated for the growth failure of children due to endogenous
growth hormone deficiency (GHD).
is indicated for short stature in children caused by Noonan syndrome.
is indicated for short stature or growth disorders in children caused by
SHOX gene defect.
is indicated for short stature in children caused by achondroplasia.
is indicated for short bowel syndrome in adults receiving nutritional
support.
is indicated for treatment of severely burned patients.

When reconstitution, 1ml sterile water for injection should be injected along the bottle
wall, then swirl the vial with a gentle rotary motion until the contents are completely
dissolved, do not shake violently.

should not be used in patients whose epiphysis had been closed.
should not be used in patients in acute shock stage with severe infection.
should not be used in patients with known allergy to growth hormone or its protective agents.
should not be used in cancer patients with active neoplasia. Any existing malignancy should be inactive and complete tumor treatment prior to growth hormone therapy. GH therapy should be discontinued if evidence of tumor recurrence. Because growth hormone deficiency may be an early sign of the presence of pituitary tumors (or other rare brain tumors), therefore, the presence of such tumors should be excluded before treatment. Growth hormone should not be used in any patients with potential intracranial tumor progression or recurrence.
should not be used in patients with complications of the following acute critical diseases: open heart surgery, abdominal surgery, or multiple trauma.
should not be used when acute respiratory failure occurs.
should not be used in patients with proliferative or severe nonproliferative diabetic retinopathy are contraindicated.

1. rhGH therapy should be conducted on exactly diagnosed GHD patients under
advice of experienced doctor.
2. Impaired glucose tolerance and glycuresis: Monitoring blood sugar levels regularly
in all patients treated with growth hormone, especially those with diabetes risk factors,
such as obesity, turner syndrome, or a family history of diabetes, and blood glucose
levels during growth hormone therapy in patients with type 1 or 2 diabetes or
impaired glucose tolerance should be closely monitored. The dosage of
antihyperglycemia drugs (such as insulin or oral or injectable drugs) in these patients
needs to be adjusted.
3. Hypoadrenia: Patients who were previously diagnosed with adrenal hypofunction
and treated with glucocorticoid replacement therapy need to increase the initial or maintenance dose of growth hormone therapy.
4. Thyroid gland function should be tested regularly because clinical hypothyroidism
may occur to some patients during rhGH therapy. For those hypothyroid, thyroid
supplementation is necessary for ensuring the therapeutic effects of rhGH.
5. If lameness, hip or knee pain occur during the treatment period of growth hormone,
it is necessary to evaluate whether there is slippage of epiphyseal plate of femoral
head.
6. Bow legs may worsen in patients with growth hormone therapy for cartilage
dysplasia with bow legs. Such patients should be closely observed when taking
medicine. If any abnormality is found, the administration should be stopped and
appropriate measures should be taken.
7. In the treatment of patients with cartilage hypoplasia with macroporous stenosis by
growth hormone, this class of drugs may contribute to the deterioration of symptoms,
administration can only be considered when it is judged that the benefit of drugs for
improving short stature is greater than the risk of deterioration of spinal stenosis /
macroporous stenosis. Regular monitoring, such as MRI, should be fully carried out,
and the administration should be promptly stopped when the deterioration of
macropore stenosis is observed.
8. In the treatment of short bowel syndrome in adults, tissue swelling (especially
swelling of the hands and feet) due to increased fluid retention, musculoskeletal
discomfort (pain, swelling and/or stiffness) due to joint pain, and carpal tunnel
syndrome may occur. Symptoms of fluid retention and joint pain may generally be
relieved by themselves, or analgesic therapy or dose adjustment may be alleviated
according to the degree of onset. Stop growth hormone therapy if the dose reduction
still unable to relieve carpal tunnel syndrome.
9. Blood glucose may be increased transitorily during the treatment of severe burns,
but it could be returned to normal with the continued therapy of rhGH or with
additional treatment of insulin. The treatment with rhGH should be stopped while
blood glucose level is greater than 11.1mmol/L for over 3 days with additional
treatment of insulin.
10. Injection site should often variation in case lipoatrophy.
11. Progression of scoliosis can occur in rapidly growing patients. Because growth hormone therapy can increase the growth rate, patients with a history of scoliosis
should be monitored for scoliosis progression during growth hormone therapy.
Growth hormone therapy has not been shown to increase the incidence of scoliosis.
Noonan syndrome itself is often accompanied by skeletal abnormalities such as
scoliosis. In clinical studies of SHOX gene defects treated with growth hormone,
more patients developed scoliosis in the growth hormone treatment group than in the
control group (Clinical trial information from the similar product manual approved for
marketing abroad). Caution should be given to these abnormalities that may occur
during growth hormone therapy.
12. Congenital heart disease is the main manifestation of Noonan syndrome. There is
no evidence that somatrophin induces ventricular hypertrophy or exacerbates existing
ventricular hypertrophy. Children with Noonan syndrome and severe heart disease
should be adequately evaluated before taking growth hormone therapy to determine
whether heart disease severity has a significant effect on growth.
13. The size and number of skin nevi, gynecomastia, joint pain, especially in patients
with SHOX gene defects, were monitored during treatment. Caution should be given
to these abnormalities that may occur during growth hormone therapy.
14. Acute critical illness: There have been reports of increased mortality after
somatropin therapy for several reasons, such as open heart surgery, abdominal surgery,
multiple accidental trauma, or acute respiratory failure. The safety of continued use of
approved doses of growth hormone in patients with these diseases has not been
established. Therefore, the potential benefits and risks of continuing somatropin
therapy in patients with acute critical illness need to be assessed.
15. Tumors: Childhood cancer survivors treated with craniocerebral radiation for their
first tumor have been reported to have an increased risk of developing a second tumor
with secondary growth hormone deficiency and growth hormone therapy. Intracranial
tumors, especially meningiomas, are the most common second tumors. All patients
with growth hormone deficiency secondary to intracranial tumors are routinely
monitored for tumor progression or recurrence during growth hormone therapy.
16. Doctors should weigh the risks and benefits of growth hormone therapy in
children with short stature who have an increased risk of developing tumors due to a
rare genetic mutation. If somatropin therapy has been initiated, attention should be
paid to monitoring the development of the tumor.
17. Leukemia: Occurs in a few patients with growth hormone deficiency, some of
whom have been treated with growth hormone. But there is no evidence that treatment
with somatropin increases the incidence of leukaemia in patients without predisposing
factors.
18. Intracranial hypertension: Fundoscopy for papilloedema should be performed
routinely prior to the initiation of somatropin therapy to rule out preexisting papillary
edema of the optic nerve and should be performed periodically during therapy. If
papilloedema is confirmed during therapy, the growth hormone treatment should be
discontinued. If the increase in intracranial pressure induced by growth hormone is
confirmed, the growth hormone therapy can be resumed at a lower dose after the signs
and symptoms related to the increase in intracranial pressure have been relieved.
19. Severe allergy: Patients and caregivers should be informed of the possibility of
allergic reactions. If allergic reactions occur, they should be treated in time.
20. Fluid retention: its clinical manifestations (e.g., edema, postoperative myalgia
syndrome, nerve compression syndrome such as carpal tunnel syndrome/tactile
abnormalities) are transient and dose-dependent.
21. Laboratory examination: Serum levels of phosphorus, alkaline phosphatase,
parathyroid hormone, and IGF-1 may be elevated during growth hormone therapy.
22. Pancreatitis: Children treated with growth hormone rarely report pancreatitis, and
some evidence suggests that children are at higher risk than adults. Any patients
treated with growth hormone, especially children with abdominal pain symptoms,
should consider the possibility of pancreatitis.
23. Careful use of athletes.

No studies on the effects on the ability to drive and use machines have been
performed. However, depending on the sensitivity of the individual patient, the
medical may have an effect on the speed of reaction which could impair certain
operations.

The following information on possible adverse reactions to the use of growth
hormone was obtained from the literature data of similar products abroad, including those that occurred in clinical trials and those reported in spontaneous reports after
marketing.
Data from foreign clinical trials of growth hormone products: since clinical trials are
conducted under different conditions, the incidence of adverse reactions of one type of
growth hormone preparation is often not comparable with that of another type, and the
incidence of adverse reactions is not reflected in the actual clinical use of the
situation.
Growth hormone is a kind of protein medicine that produces antibodies in a few
patients. Studies have shown that a small number of patients who have not been
treated with somatrophin have developed somatrophin-specific antibodies at
concentrations of less than 2 mg/L after 6 months of somatrophin therapy. Long-term
injection of recombinant human growth hormone, if produced antibody, but antibody
binding force is low, there is no definite clinical significance. However, if the
antibody binding force exceeds 2mg/L, the efficacy may be affected. In addition to the
evaluation of compliance and thyroid function, any patient who does not respond to
growth hormone therapy should be tested for growth hormone antibody.
Children
Growth hormone deficiency
In studies of growth hormone deficiency in children, the following adverse reactions
are rare, such as injection site reactions, including injection site pain, swelling,
fibrosis, nodules, rashes, inflammation, pigmentation or bleeding; adipose atrophy;
headache; hematuria; hypothyroidism; transient mild hyperglycemia; and mild and
transient edema.
Noonan syndrome
A prospective, randomized, parallel dose controlled trial for 2 years, 21 patients with
Noonan syndrome aged 3-14 years were enrolled. The dosage of the treatment is
0.033 mg/kg/day and a dose of 0.066mg/kg/day, respectively. After completing 2
years of clinical trials, continuous application of growth hormone therapy to lifetime
high. There was no difference in adverse events between the two dose groups.
Congenital heart disease is a congenital disease associated with Noonan syndrome,
There was no evidence during the study that growth hormone induced ventricular
hypertrophy or exacerbated existing ventricular hypertrophy (as determined by
B-ultrasound). Children with severe heart disease were excluded from the study before it started, so the safety of growth hormone therapy for children with Noonan
syndrome with severe heart disease is unknown. In children who treated with a dose
of 0.033mg/kg/day, scoliosis occurred in 1 case; In children who treated with a dose
of 0.066mg/kg/day, scoliosis occurred in 4 case. For growth hormone therapy, the
average serum 1GF-1 level did not exceed + 1, and the average serum 1GF-1 level
was low at baseline, and gradually normalized during the treatment.
SHOX gene defect
A randomised, openness study for 2 years, the adverse reactions related to growth
hormone therapy and of clinical significance are shown in Table 1. After 1 year, the
average fasting glucose level in the growth hormone group was close to the baseline
and within the normal range. None of the patients had diabetes or fasting glucose
concentration above the normal range. In the second year of the study, the growth
hormone treated group and the untreated group, the proportion of patients whose
IGF-1 concentration exceeded the mean of the same age and gender 2SD at least once
was 10/27(37.0%) and 0/24(0%), respectively. The proportion of patients whose
IGF-3 concentration exceeded the mean of the same age and gender 2SD at least once
was 16/27(59.3%) and 7/24(29.2%), respectively.
Achondroplasia
In a safety assessment study of 46 subjects, 25 patients (54.3%) had side effects of
abnormal changes in clinical examination. The main adverse reactions were bow legs
deterioration (2 cases: 4.3%), OGTT abnormality (10 cases: 21.7%), eosinophilia (6
cases: 13.0%), HbA1 increase (6 cases: 13.0%). In the safety assessment of 103
subjects using the performance survey, 17 cases (16.5%) had side effects of abnormal
changes in clinical examination. The main side effects were atypical lymphocyte
increase (3 cases: 2.9%), spinal stenosis (3 cases: 2.9%), increase of CK (CPK)
increased (2 cases: 1.9%).
Adult
Short bowel syndrome
In a double-blind, randomized, placebo-controlled clinical trial, 32 patients treatment
with growth hormone for 4 weeks. Among the 41 patients enrolled in the trial: 16
patients received growth hormone (0.1 mg/kg/day) + supportive diet; 16 patients
received growth hormone (0.1 mg/kg/day) + supportive diet + oral glutamine (30
g/day); 9 patients received placebo + supportive diet + oral glutamine (30g days).
More than 20 percent of patients treated with growth hormone alone, the incidence of
the most common adverse reactions was higher than that of the control group,
including , facial edema, joint pain, injection site pain, gastrointestinal flatulence and
abdominal pain (see Table 2 below). After 4 weeks of growth hormone treatment, the
patient was discharged from the hospital, continued on a supportive diet with oral
supplementation of glutamine or glutamine placebo, and returned to the clinic for
reevaluation 12 weeks later. No new adverse drug reactions were found during
follow-up.
Post-marketing data of foreign growth hormone products: the adverse reactions
reported in spontaneous post-marketing reports were from people with uncertain
sample size, and the incidence of adverse reactions or their correlation with drug
exposure could not be reliably assessed.Therefore, the occurrence of the following
adverse reactions may be different in patients with actual use of growth hormone
therapy.
Severe allergy: It is very rare and has been reported in the foreign literature that
severe systemic allergic reactions, including anaphylaxis and angioneurotic edema,
have occurred after therapy.
Nervous system: Headache (common in children, occasional in adults).
Skin: Increased size and number of skin nevi, especially in patients with SHOX gene
defects.
Endocrine: Gynecomastia.
Gastrointestinal tract: Pancreatitis.When patients develop abdominal pain, especially
in children, it should be considered for pancreatitis.
Metabolism: Some patients have newly developed type 2 diabetes.
Tumor: Leukemia has been reported in a small number of children treated with
growth hormone. However, it is not certain whether it is related to the treatment of
growth hormone, the pathology of the growth hormone deficiency disease itself or
other related treatments (such as radiotherapy).At present, it has not been confirmed
that the treatment of growth hormone is related to the leukaemia.

1. Acute overdose could lead initially to hypoglycaemia and subsequently to
hyperglycaemia.
2. Long term over-dosing could result in signs and symptoms of gigantism and/or
acromegaly consistent with the known effects of rhGH excess.

Pharmacodynamic properties
Recombinant human growth hormone (rhGH) is secreted by growth hormone (GH)
secreting cells containing eosinophilic granules in the anterior pituitary. It is a peptide
hormone composed of 191 amino acids. Recombinant human growth hormone (rhGH)
was produced by the highly efficient expression of rhGH gene in escherichia coli. The
amino acid content, spatial conformation and sequence of the active substance is
identical to that of rhGH of pituitary origin. Ansomone® exerts the same actions of
endogenous human growth hormone. It can stimulate proliferation and differentiation
of epiphysis chondrocyte, stimulate growth of cartilage matrix cells, stimulate
proliferation and differentiation of osteoblast; thus accelerate the liner growth rate and
improve epiphysis width. Ansomone® can promote protein synthesis in whole body;
reverse the negative nitrogen equilibrium caused by wound and surgery; correct the
hypoproteinemia due to severe infection or hepatocirrhosis; stimulate synthesis of
immune globin and proliferation of lymphadenoid, macrophage and lymphocyte, thus
enhance the ability of infection resistance; stimulate proliferation of collagenocyte,
fibroblast and macrophage in sites of burn and surgery, thus accelerate wound healing;
promote synthesis of cadiocytes, thus improve cardiac contractility and reduce cardiac
oxygen consumption; regulate lipometabolism, thus depress serum cholesterol and
low density lipopretein’ s level; complement insufficiency or deficiency of growth
hormone, regulate adult ’ s lipomeabolism, osteometabolism, heart and kidney
function.

Pharmacokinetic properties
1. It is reported that the equal pharmacological effect could be achieved via
subcutaneous (SC) or intramuscular (IM) administration. Even though SC may lead a
higher concentration of GH in plasma, IM could also yield the same IGF-I level. The
absorption of GH is the relatively slow, Cmax often occurs at 3-5 hours after injection.
Clearance of GH is via liver and kidney, the half-life of clearance is about 2-3 hours.
Uncatabolized GH excreted in urea is almost immeasurable. All of the GH in
circulation system exists as a complex form with GH binding proteins that make the
half-life of GH prolonged.
2. Almost all GH in the circulation binds to the high-affinity GH-binding protein
(hGHBP), This compound prolongs the half-life of GH in serum, and the choice of
injection time during the day will not affect the serum GH concentration.
There is no study on this item.
5.3 Preclinical safety data
In the long-term toxicity test, they were divided into four dose groups, namely high,
medium, low and control groups. 20 healthy female SD rats were divided into
high-dose group (financial equivalent to 50 times of the clinical dose of appointment
(3.125 mg / kg), medium dose and low-dose group (25 times (1.563 mm / kg) and 8
times (0.500 mg / kg). RHuGH was used for intramuscular injection (IM) for 42
consecutive days（14 days after drug withdrawal, the toxic reaction and recovery of
rats were observed. The results showed that the body weight of male and female rats
increased in 42 days after administration of high-dose and medium dose.
In addition, the blood Glu content of high-dose rats increased in 42 days after
administration of rhGH (p < 0.05). These changes belong to pharmacodynamic effect
and can be recovered after 14 days of drug withdrawal. Therefore, it is considered that
rhGH is a low toxicity growth promoting drug.

List of excipients
Mannitol
Glycine
Sodium-bicarbonate
Water for injection

incompatibilities
1. 11β-Hydroxysteroid dehydrogenase type 1 (11β-HSD1) : In fat and liver tissues,
conversion of adrenocortical ketone to active metabolite cortisol requires microsomal enzymes 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1). Endogenous and exogenous growth hormone can inhibit 11β-HSD1, therefore, untreated growth
hormone deficiency patients with 11β-HSD1 and blood cortisol will be relatively
increased. The treatment with growth hormone inhibited 11 β-HSD1 and decreased
the concentration of cortisol in the blood. Therefore, patients with previously
undiagnosed central (secondary) hypoadrenalinism may develop and be diagnosed
with growth hormone therapy and may require glucocorticoid replacement therapy. In
addition, patients who have been diagnosed with adrenal dysfunction and are
receiving glucocorticoid replacement therapy may require an increase in maintenance
or stress dose after initiation of growth hormone therapy; especially in patients treated
with cortisone acetate and prednisone because these hormones have to rely on 11
β-HSD1 of activity to convert into their bioactive metabolites.
2. Pharmacological dose of glucocorticoid therapy and hyperphysiological dose of
glucocorticoid therapy: Excessive glucocorticoid therapy can inhibit the actions of
rhGH. Patients receiving concomitant glucocorticoid therapy should have their dose
carefully adjusted, so that hydrocortisone dosage would be lower than 10-15 mg/m2
of body surface during rhGH therapy.
3. Non-androgenic steroids: Simultaneous using of non-androgenic steroid during
rhGH therapy can accelerate growth rate.
4. Drugs metabolized by cytochrome P450 (CYP450) : Limited published data shows
that, somatropin administration may increase the clearance of compounds known to
be metabolised by cytochrome P450 isoenzymes. The clearance of compounds
metabolised by cytochrome P450 3A4 (e.g. sex steroids, corticosteroids,
anticonvulsants and cyclosporine) may be increased resulting in lower plasma levels
of these compounds. The clinical significance of this is unknown.
5. Oral estrogen: Oral estrogen may reduce the response of blood igf-1 to growth
hormone therapy, therefore, in women taking oral oestrogens, a higher dose of
somatropin may be required to achieve the treatment goal.
6. Insulin and/or other hypoglycemic medications: Patients taking insulin for diabetes
mellitus should be carefully monitored during treatment with somatropin. Because
rhGH may induce a state of insulin resistance, an adjustment of the insulin dose.

24 months

Keep at 2~8℃ away from light. The reconstituted solution can be stored at 2~8℃
for 48 hours, do not be frozen.

Tube-type Bottle, 1 vial/box.

1. The recommended dosage of Ansomone® for the treatment of growth retardation in
children due to endogenous growth hormone deficiency is 0.1~0.15 IU/kg/day
(0.033~0.050mg/kg/day), subcutaneous administration, once daily. However, the
dosage varies from person to person. Treatment course: it is recommended to use until
the epiphysis is closed, or modified according to experienced doctor’s suggestion.
2. The recommended dosage of Ansomone® for the treatment of short stature in
children caused by Noonan syndrome is 0.1~0.2 IU/kg/day (0.033~0.066 mg/kg/day),
subcutaneous administration, once daily. Treatment course: Use until epiphysis is
closed is recommended, or modified according to experienced doctor’ s suggestion.
3. The recommended dosage of Ansomone® for the treatment of short stature or
growth disorders in children caused by SHOX gene defect is 0.15 IU/kg/day (0.05
mg/kg/day) or 1.05 IU/kg/week (0.35 mg/kg/week), subcutaneous administration.
Treatment course: Use until epiphysis is closed is recommended, or modified
according to experienced doctor’ s suggestion.
4. The recommended dosage of Ansomone® for the treatment of short stature in
children caused by achondroplasia is 0.15 IU/kg/day (0.05 mg/kg/day) or 1.05
IU/kg/week (0.35 mg/kg/week), subcutaneous administration. Treatment course: Use
until epiphysis is closed is recommended, or modified according to experienced
doctor’ s suggestion.
5. The recommended dosage of Ansomone® for the treatment of short bowel
syndrome in adults receiving nutritional support is 0.3 IU/kg/day (0.1 mg/kg/day),
subcutaneous administration, once daily. The maximum daily dose should not exceed
24 IU (8mg). Treatment course: Continuous treatment for 4 weeks is recommended.
Fluid retention and arthralgia / carpal tunnel syndrome occurred during treatment, the
dosage can be adjusted according to the degree of occurrence: For moderate cases, use
analgesics for symptomatic treatment or reduce the recommended dose to 0.15IU/kg (0.05mg/kg), subcutaneous administration, once daily, and the maximum daily dose is 12 IU (4mg); for severe cases, stop using growth hormone for 5 days at most. After
the symptoms disappear, inject subcutaneously once a day for 0.15 IU/kg (0.05mg/kg),
and repeat the treatment with maximum daily dose of 12 IU (4 mg). If severe cases
occur again or do not disappear within 5 days, stop using growth hormone treatment.
6. The recommended dosage of Ansomone® for the treatment of severe burn is
0.2~0.4 IU/kg/day(0.067~0.133 mg/kg/day) subcutaneous administration for 2 weeks.